Journal article
Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo
Human gene therapy, v 20(10), pp 1143-1156
Oct 2009
PMID: 19530914
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Plasmid-encoded DNA vaccines appear to be a safe and effective method for delivering antigen; however, the immunogenicity of such vaccines is often suboptimal. Cytokine adjuvants including interleukin (IL)-12, RANTES, granulocyte-macrophage colony-stimulating factor, IL-15, and others have been used to augment the immune response against DNA vaccines. In particular, IL-15 binds to a unique high-affinity receptor, IL-15Rα; is
trans
-presented to CD8
+
T cells expressing the common βγ chain; and has been shown to play a role in the generation, maintenance, and proliferation of antigen-specific CD8
+
T cells. In this study, we took the unique approach of using both a cytokine and its receptor as an adjuvant in an HIV-1 vaccine strategy. To study IL-15Rα expression, a unique monoclonal antibody (KK1.23) was generated to confirm receptor expression
in vitro
. Coimmunization of IL-15 and IL-15Rα plasmids with HIV-1 antigenic plasmids in mice enhanced the antigen-specific immune response 2-fold over IL-15 immunoadjuvant alone. Furthermore, plasmid-encoded IL-15Rα augments immune responses in the absence of IL-15, suggesting its role as a novel adjuvant. Moreover, pIL-15Rα enhanced the cellular, but not the humoral, immune response as measured by antigen-specific IgG antibody. This is the first report describing that IL-15Rα itself can act as an adjuvant by enhancing an antigen-specific T cell response. Uniquely, pIL-15 and pIL-15Rα adjuvants combined, but not the receptor α chain alone, may be useful as a strategy for generating and maintaining memory CD8
+
T cells in a DNA vaccine.
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Details
- Title
- Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo
- Creators
- Kimberly A Kraynyak - Department of Pathology and Laboratory MedicineMichele A Kutzler - Division of Infectious Diseases and HIV MedicineNeil J Cisper - Department of Pathology and Laboratory MedicineDominick J Laddy - Department of Pathology and Laboratory MedicineMatthew P Morrow - Department of Pathology and Laboratory MedicineThomas A Waldmann - National Cancer InstituteDavid B Weiner - Department of Pathology and Laboratory Medicine
- Publication Details
- Human gene therapy, v 20(10), pp 1143-1156
- Publisher
- Mary Ann Liebert, Inc; 140 Huguenot Street, 3rd FloorNew Rochelle, NY 10801USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000271026800006
- Scopus ID
- 2-s2.0-75649145032
- Other Identifier
- 991014877792304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Genetics & Heredity
- Medicine, Research & Experimental